Postmortem Validation of Quantitative Susceptibility Mapping

Quantitative susceptibility mapping (QSM) is a novel method for the non-invasive assessment of a basic physical property by magnetic resonance imaging (MRI) in vivo. Iron accounts for a substantial share of the magnetic susceptibility observed in the human brain tissue and increased iron accumulation is linked to neurodegenerative processes. While iron is paramagnetic, neuronal fibers are diamagnetic and it remains still unclear how their myelin content, ratio of lipids to proteins, diameter of myelinated nerve axons, fiber bundle geometry as well as other non-myelin related factors attribute to the magnetic susceptibility. We hypothesize that by modeling magnetic susceptibility, the determinants underlying QSM can be disentangled, which is currently not possible using in vivo MRI. Ten postmortem brains from control subjects and 10 brains from patients with multiple sclerosis (MS) will undergo extensive MRI. Complementary to MRI, tissue specimens will be analyzed by mass spectrometry, magnetometry, histologic staining, as well as transmission electron microscopy. The magnetic susceptibility observed by MRI will be explained by the aforementioned contributors. This project will quantify several biophysical mechanisms of magnetic susceptibility, and ultimately allow non-invasive QSM in patients with neurological diseases in vivo.